It is generally accepted that many of the new pharmaceutically active molecules are insoluble or poorly soluble in water. In order to improve the bioavailability of drugs that exhibit dissolution rate limited oral absorption profiles or to simplify the formulation process, it often becomes necessary to administer the drug in form of a solution or a suspension. Such an approach would then mandate the use of suitable solubilizers in which the pharmaceutical active agent can be fully or partially dissolved. The liquid formulation would then have to be encapsulated in a suitable capsule shell (i.e., hard gelatin, soft gelatin, HPMC hard shell, etc.) to be administered as a solid dosage form. There is often the problem of lack of capsule shell integrity in presence of effective non-aqueous solubilizers such as N-methyl-2-pyrrolidone (NMP) and pyrrolidone derivatives. The capsule shell is either completely dissolved in the solubilizer or it softens as a result of the strong solubilizing properties of the non-aqueous solubilizers. Such deformities would lead to product failures and would limit further dosage formulation development.
The problem of gelatin capsule stability has been addressed by many (see U.S. Pat. Nos. 2,780,355, 4,497,157, 4,777,048, 4,780,316, 5,037,698 and 5,376,381), these innovations have generated different solutions tailored to specific wall destabilizing agents such as hygroscopic and deliquescent components, ethanol, lubricants, salts, etc.
Thus there is a need for oral capsule formulations, containing non-aqueous solubilizers, with increased physical stability.
The present invention provides such a capsule formulation with increased physical stability for oral administration.